These studies are designed to assess the capacity of hormonally active chemicals to alter hepatic metabolism and to determine if changes in the endocrine environment can influence hepatic enzyme development and hepatotoxic responses. The rat is used as the experimental model. The initial focus has involved sex differentiation of microsomal hemoproteins in rat liver and the response of hepatic monooxygenase to cadmium; male liver monooxygenases activities are repressed by cadmium whereas female enzymes are unaffected by this treatment. Male sensitivity to cadmium appears to reflect the amount of cadmium-sensitive hemoproteins (detected on SDS gels and by hemoprotein synthesis/degradation studies) which are under hypophyseal control. Additionally, hepatic enzymes and specific forms of cytochrome P-450 are under varied forms of control by the hypophyseal-gonadal axis. Includes Z01 ES 70135-03 LOFT.